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Biomedical subjects

D N Gerding

Publications and source records attributed to D N Gerding.

At least 181 records · Page 10Linked to original sources
PubMed1977

Evaluation of three newer methods for investigating protein interactions of penicillin G.

THE INTERACTION OF PENICILLIN G WITH HUMAN SERUM PROTEINS WAS EVALUATED BY THREE DIFFERENT TECHNIQUES: rate of dialysis, cross-linked dextran exclusion, and ultracentrifugation. The rate-of-dialysis technique demonstrated that penicillin G binding to serum was immediate but incompletely reversible. Cross-linked dextran adsorbed or trapped significant amounts of penicillin G, necessitating correction factors of more than 10%. Ultracentrifugation was found to be the most reliable method for quantitative protein-binding determinations of penicillins.

Blood Proteins↗
PubMed1977

Gentamicin intravenous infusion rate: effect on interstitial fluid concentration.

To assess the possible role of intravenous (i.v.) infusion rate as a determinant of degree and rate of interstitial fluid penetration, six rabbits, each with four intraperitoneal implanted capsules, were studied by crossover design after a single dose of 1.7 mg of gentamicin per kg by either slow 2.5-min i.v. bolus or 30 min i.v. infusion. The mean serum peak antibiotic level after slow bolus was 17.4 mug/ml. After 30 min of infusion, mean serum peak was 8.3 mug/ml (P < 0.025). Mean capsule fluid antibiotic levels at 30 min, 1, and 2 h were 0.9 mug/ml, 1.6 mug/ml, and 1.8 mug/ml, respectively, after slow bolus and 0.6 mug/ml, 0.9 mug/ml, and 1.3 mug/ml after 30-min infusion (P < 0.05 at 30 min, P < 0.001 at 1 h, and P < 0.05 at 2 h). Comparison of capsule levels beyond 2 h revealed no significant differences, and peak capsular concentrations achieved by the two methods were similar. Slow 2.5-min i.v. bolus administration of gentamicin established higher interstitial fluid levels during the first 2 h of therapy and may be the preferred mode of delivery when rapid extravascular penetration is desired.

Animals↗
PubMed1977

Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis.

Thirty-six paired specimens of serum and ascitic fluid from 21 patients with peritonitis and ascites, most with sponetaneous bacterial peritonitis and alcoholic cirrhosis, were assayed for antibiotic content. Antibiotics assayed and number of determinations were gentamicin, 14; tobramycin, 7; ampicillin, 5; clindamycin, 3; penicillin G, 2; cephalothin, 2; chloramphenico, 2; and cefazolin, 1. In 31 pared specimens the ascitic fluid antibiotic concentration was about one half or more of the simultaneous serum level and in 17 assays exceeded 90% of the serum level. All antibiotics studied penetrated ascitic fluid equally well. Clinical response to antibiotic therapy was good in 12 of 16 patients with culture-proven bacterial peritonitis. Antibiotic levels in ascitic fluid exceeded the minimal inhibitory concentration of the infecting organisms in all but one patient who responded. Direct intraperitoneal instillation of antibiotics does not appear to be necessary routinely; however, there may be an initial lag of several hours before antibiotic concentrations is ascites achieve therapeutic levels.

Adult↗
PubMed1976

Increased dosage requirements of gentamicin in burn patients.

In 14 burn patients treated for serious Gram-negative infections, the use of the previously recommended gentamicin dose of 5 mg/kg/day was found to result in subtherapeutic serum concentrations (peak concentration less than 4 mg/L). The gentamicin half-life was found to be unusually short especially in the younger burn patients. Because of this shorter half-life the dosage interval was decreased to 4 hours to prevent extended periods of subtherapeutic serum concentrations. In addition, the daily dose of gentamicin was increased to achieve therapeutic peak concentration. Individualizing each patient's gentamicin regimen was thought to be instrumental in the favorable response of two patients with Pseudomonas ecthyma gangrenosum. The results of this study would strongly support the measurement of serum gentamicin levels in all burn patients with life-threatening infection. The gentamicin dosage regimen should then be individualized for each patient to provide optimal peak concentrations. In addition, patients demonstrating a short drug half-life may require a decreased dosage interval to prevent prolonged periods of sub-therapeutic concentrations.

Adolescent↗
PubMed1976

Antibiotic penetrance of ascitic fluid in dogs.

Antibiotic concentrations in ascitic fluid after parenteral therapy may be important in the treatment of peritonitis. We have created ascites in dogs by partial ligation of the inferior vena cava. Ascitic fluid volume was measured at the time each antibiotic was administered. Nine antibiotics were studied in the same three dogs. Antibiotic concentration in ascitic fluid was found to vary inversely with ascites volume. Percentage of penetration (ratio of ascites peak to serum peak x100) ranged from 5.8 to 65% among the drugs studied. Only metronidazole showed a statistically significant higher percentage of penetration than other antimicrobials. Concentrations in ascitic fluid after single doses of cephalothin (15 mg/kg) and the aminoglycosides (2 mg/kg, gentamicin and tobramycin; 7.5 mg/kg, amikacin and kanamycin) did not exceed the minimum inhibitory concentration of many gram-negative rods and may justify the use of higher than usual initial parenteral doses, or possibly initial intraperitoneal administration in seriously ill patients.

Aminoglycosides↗
PubMed1976

Cephalosporin and aminoglycoside concentrations in peritoneal capsular fluid in rabbits.

To study the penetration of antibiotics into peritoneal tissue fluid, a subcutaneous tissue capsule model was modified by implanting multiple, perforated spherical capsules in the peritoneal cavity of rabbits. Capsules became vascularized, encased in connective tissue, and filled with fluid having a mean protein concentration of 3.6 g/100 ml. Capsular fluid was obtained by percutaneous needle aspiration and assayed for antibiotic by the disk plate bioassay technique. Cephalosporins were administered intramuscularly at a dose of 30 mg/kg. Mean peak concentrations of cephaloridine and cefazolin were significantly higher than cephalothin and cephapirin in capsular fluids, but the percent penetration (ratio of capsular mean peak to serum mean peak) ranged from 8.7 to 16.9% and was not significantly different among the cephalosporins. At 24 h the capsular concentration of cefazolin was significantly greater than for the other cephalosporins (P < 0.001). Lower rabbit serum protein binding observed at high in vivo concentrations may have enabled cefazolin to penetrate capsular fluid, but in vitro protein binding studies did not confirm a decrease in serum protein binding at high concentrations within the clinical range. Kanamycin and amikacin showed comparable capsular fluid peak concentrations as did gentamicin and tobramycin. The percent penetration ranged from 15.2 to 34.5% for the aminoglycosides. The only statistical difference was that amikacin penetration was significantly higher than that for tobramycin. Mean capsular concentrations of amikacin, cefazolin, and cephaloridine compared most favorably with the minimum inhibitory concentration of gram-negative bacilli at the dosages used in this study.

Aminoglycosides↗
PubMed1976

Pasteurella multocida peritonitis in hepatic cirrhosis with ascites.

Two patients with spontaneous Pasteurella multocida peritonitis in association with cirrhosis and ascites are described. Both patients had close contact with domestic animals, but neither had been bitten. Both patients died, but only one as a result of his infection. We are aware of only one previous report of cirrhosis with spontaneous peritonitis caused by this organism. P. multocida should be considered as a possible cause of peritonitis in cirrhotic patients with a history of close contact with animals, particularly cats.

Animals↗
PubMedDate not supplied

Antibacterial activity of cefoperazone and cefoperazone plus sulbactam in a neutropenic site model.

Efficacy of cefoperazone versus cefoperazone plus sulbactam was studied in a rabbit neutropenic site infection model against a broad range of clinical isolates including six isolates each of staphylococci, enterococci, pneumococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Therapy of cefoperazone plus sulbactam demonstrated enhanced efficacy against the staphylococci, pseudomonads, and Enterobacteriaceae. The activity of cefoperazone against enterococci and pneumococci was not enhanced or inhibited by the addition of sulbactam. Increased concentrations of cefoperazone found at the infection sites when sulbactam was added to the therapeutic regimen indicates that sulbactam provided a protection to cefoperazone from beta-lactamases produced by staphylococci and Enterobacteriaceae. The combination improved the efficacy of cefoperazone in this animal model.

Animals↗
PubMedDate not supplied

GyrA sequence analysis of Staphylococcus aureus and methicillin-resistant S. aureus strains selected, in vitro, for high-level ciprofloxacin resistance.

Four methicillin-susceptible Staphylococcus aureus and eight methicillin-resistant S. aureus (MRSA) isolates, all of which were ciprofloxacin susceptible (MIC < 2.0 micrograms/ml) were manipulated, in vitro, to achieve high-level ciprofloxacin resistance by means of up to 14 passages onto media containing increasing concentrations of ciprofloxacin. Resistance to ciprofloxacin at a concentration of at least 512 micrograms/ml was achieved in all 12 isolates tested. This resistance was continually detected during weekly passage on antibiotic-free media for 12 weeks. The parent and daughter cells from four strains had their gyrA sequenced from amino acid (aa) codons 70-100, the region of previous mutations in high level quinolone-resistant S. aureus. Mutations at aa codon 84 were seen in three of four strains, but appeared at varying levels of ciprofloxacin resistance. High-level resistance of S. aureus and MRSA to ciprofloxacin can be developed in vitro using multiple exposures to incremental concentrations of the drug. It is apparently due to multiple mechanisms and, once established, remains stable over time.

Ciprofloxacin↗
PubMedDate not supplied

Medical technologists using molecular epidemiology as part of the infection control team.

Two medical technologists were appointed as permanent members of a new epidemiology section in the diagnostic microbiology laboratory of a large Veterans Administration Medical Center in the fall of 1989. These positions accounted for 9% of the total microbiology staff and were created on a temporary basis 2 years earlier from a need to have dedicated technical expertise for use in the culture, isolation, and typing of nosocomial organisms. The technologists have evaluated outbreaks due to Clostridium difficile, methicillin-susceptible Staphylococcus aureus, and Serratia marcescens, and have begun work on a methicillin-resistant Staphylococcus aureus (MRSA)-typing scheme. Their major responsibility has been the development and application of molecular biology techniques for the typing of nosocomial isolates, including restriction enzyme analysis of genomic DNA, plasmid profiling with and without restriction enzyme analysis, ribosomal RNA probing of restricted genomic DNA, and selected DNA sequencing of target organisms. Medical supervision rests jointly between the directors of the infection control program and the microbiology laboratory. During their tenure, infections due to C. difficile have dropped from 95 cases per year to 57 cases annually, treatment of MRSA colonization with systemic agents has been curtailed, and a case control investigation involving S. marcescens was avoided. The inclusion of medical technologists in the infection control practice of large medical care facilities, particularly with the availability of molecular epidemiologic techniques and the emergence of increasing numbers of multiply-drug-resistant pathogens, will become an essential component of these programs.

Bacterial Infections↗
PubMedDate not supplied

Tissue penetration of the new quinolones in humans.

Data on the penetration of new quinolones into selected extravascular sites in humans, i.e., blister fluid, sputum, prostatic secretions, cerebrospinal fluid, aqueous humor, bone, prostate tissue, and cells, are reviewed and the data presented in tabular form. Published reports indicate that penetration into all sites, including intracellular sites, is high and exceeds that achievable for other commonly used antimicrobial agents, including penicillins, cephalosporins, and aminoglycosides. Available clinical treatment data support the expected favorable outcome predicted by the high extravascular concentrations achieved with quinolones.

4-Quinolones↗
PubMedDate not supplied

Influence of protein binding of antibiotics on serum pharmacokinetics and extravascular penetration: clinically useful concepts.

Critical evaluation of existing data on binding of antibiotics to serum proteins and on pharmacokinetics provides several useful principles for administration of antibiotics. With the exception of the aminoglycosides, antibiotics distribute with total body water, and the concept of a variable apparent volume of distribution leads to incorrect assumptions about restricted extravascular penetration. Antibiotics with a high degree of binding to serum proteins are not necessarily inferior; raising a given drug's binding to serum proteins from 0 to 90% reduces the concentration of free drug in serum and tissue by only one-half. The concentration of an antibiotic in extravascular fluid is essentially constant despite the marked variability of serum levels seen during intermittent administration of the drug. An important factor in determining a successful therapeutic response is maintenance of the level of free antibiotic in extravascular fluid above the minimal inhibitory concentration for the infecting organism. Finally, the extravascular distribution, tissue binding, and free-drug concentration of an antibiotic can be accurately predicted from serum kinetics and serum protein binding.

Animals↗
PubMedDate not supplied

Corynebacterium equi: a review of 12 cases of human infection.

Corynebacterium equi, an aerobic, variably acid-fast, gram-positive "diphtheroid," is an unusual cause of pulmonary infection in immunosuppressed patients. Initially, infection with C. equi may be mistaken for a mycobacterial infection. Two cases in a two-year period were observed and compared with the 10 cases previously reported in the literature. All but one patient had pulmonary involvement, and the presentation of all other patients was typically insidious, with fatigue, fever, and nonproductive cough. Chest roentgenograms showed cavitary lesions in seven of 11 patients. Four of 12 patients had associated bacteremias, and three of 12 had subcutaneous abscesses or lymphadenitis. One of our patients developed multiple brain abscesses. Overall mortality was 25%. The organism is susceptible to vancomycin, erythromycin, aminoglycosides, and chloramphenicol. Optimal duration of antibiotic therapy and the proper role of surgery in treatment is uncertain, but relapses have been common and many weeks of antibiotic therapy have generally been required for cure.

Abscess↗